Partial GCK gene deletion mutations causing maturity-onset diabetes of the young

Aims Maturity-onset diabetes of the young (MODY) is an autosomal dominant monogenic form of diabetes, and glucokinase-maturity-onset diabetes of the young (GCK-MODY), or MODY 2, being the most prevalent type. However, the presence of copy number variants (CNVs) may lead to misdiagnoses, as genetic testing for MODY is typically reliant on sequencing techniques. This study aimed to describe the process of diagnosis in a Chinese pedigree with an exon 8-10 deletion of the GCK gene.Methods This study collected clinical data and medical history through direct interviews with the patient and reviewing relevant medical records. Sanger sequencing and whole exome sequencing (WES) were conducted over years of follow up. WES-based CNV sequencing technology was used to detect CNVs and the results were validated by multiplex ligation-dependent amplification dosage assay (MLPA). Additionally, we reviewed the previously reported cases caused by heterozygous exon deletion of the GCK gene.Results WES-based CNV detection revealed a heterozygous exon 8-10 deletion in the GCK gene within this particular pedigree after Sanger sequencing and WES failed to find causal variants in single nucleotide variations (SNVs) and small indels. The deletion was considered pathogenic according to ACMG/AMP and ClinGen guidelines. Most of the previously reported cases caused by heterozygous exon deletion or whole gene deletion of the GCK gene present similarly to GCK-MODY caused by SNVs and small indels.Conclusions This study contributed to progress in our comprehension of the mutation spectrum of the GCK gene and underscored the significance of CNV detection in the genetic testing of MODY.